P2334 - Efficacy and Safety of Linaclotide in Patients With Chronic Idiopathic Constipation: A Post Hoc Analysis of Phase 3 Clinical Study Data Assessing Primary and Additional Endpoints by Race and Ethnicity, and by Age
Advocate Health Wake Forest Medical University Charlotte, NC
Baharak Moshiree, MD1, Lin Chang, MD2, Mena Boules, MD3, Wendy Chen, PharmD4, James Wu, PhD3, Moming Li, PhD4, Paul Feuerstadt, MD5, Kyle Staller, MD, MPH6 1Advocate Health Wake Forest Medical University, Charlotte, NC; 2Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA; 3Ironwood Pharmaceuticals, Inc., Boston, MA; 4AbbVie, Inc., North Chicago, IL; 5Yale School of Medicine, PACT Gastroenterology Center, Hamden, CT; 6Center for Neurointestinal Health, Massachusetts General Hospital, Boston, MA
Introduction: Chronic idiopathic constipation (CIC) is a common gastrointestinal condition. Race-/ethnicity-related variations may influence its clinical presentation and treatment outcomes, yet published data differentiating CIC experience between these groups are limited. This post hoc analysis evaluated linaclotide (LIN) efficacy and safety in CIC patients by race and ethnicity, followed by age.
Methods: Pooled data from 4 Phase 3 randomized controlled studies (NCT00730015, NCT00765882, NCT02291679, NCT01642914) of patients who met modified Rome II/III CIC criteria and received placebo (PBO), LIN 72 µg or LIN 145 µg were stratified by race (white, Black, Asian, Other) and ethnicity (non-Hispanic, Hispanic), followed by age (< 65, ≥65 yrs). Statistical analyses assessed the complete spontaneous bowel movement (CSBM) overall responder rate (≥3 CSBM per week and ≥baseline+1 for ≥9/12 weeks; primary endpoint), 12-week change from baseline (CFB) in CIC symptoms and time to response across groups. Safety was also evaluated.
Results: Of the 2,400 CIC patients (83.3% female), there were 72.6% white (mean age: 47.9 yrs), 23.5% Black (45.0 yrs), 2.4% Asian (38.0 yrs) and 1.5% Other (42.1 yrs); 72.9% non-Hispanic (47.9 yrs) and 27.1% Hispanic (44.0 yrs). Within each race/ethnicity group, baseline bowel and abdominal symptoms were generally similar across treatment arms. The proportion of CSBM overall responders was higher for LIN than PBO across races/ethnicities, mostly irrespective of age (Figure 1). Similar trends in 12-week CFB in CIC symptoms were generally observed across races/ethnicities (Table 1). Overall, median time to improvement from baseline in CSBM weekly rate ≥1 was 3 weeks (LIN 72 µg) and 2 weeks (LIN 145 µg); in general, LIN reduced time to improvement vs PBO across races/ethnicities (Table 1). Diarrhea was the most common treatment-emergent adverse event in LIN-treated patients across races except Other (LIN 72 µg: White, 20.1%, Black, 18.3%, Asian, 7.1%, Other, 16.7%; LIN 145 µg: White, 18.9%, Black, 13.6%, Asian, 5.0%, Other, 6.3%) and across ethnicities (LIN 72 µg: Non-Hispanic, 28.3%, Hispanic, 7.3%; LIN 145 µg: Non-Hispanic, 19.0%, Hispanic, 11.4%), mostly irrespective of age.
Discussion: LIN improved CSBM responder rates and CIC symptoms, and had a similar safety profile, across most races/ethnicities and ages in CIC patients. Small sample sizes for Asian and Other groups (and some age subgroups) limit data interpretation and highlight the need to recruit more diverse populations in clinical studies.
Figure: Percentage of CSBM Overall Responders by A) Race and Ethnicity in All Patients, B) Race and Ethnicity in Patients Aged <65 Years and C) Race and Ethnicity in Patients Aged ≥65 Years.
n represents the number of patients with CSBM overall responder data available within each group. p-values are descriptive only and show the difference in responder rate obtained from Cochran-Mantel-Haenszel tests controlling for geographic region for pairwise comparisons of each LIN dose vs PBO. ‘Black’ includes patients who identified as Black or African American. ‘Other’ includes patients who identified as having more than one race or being American Indian or Alaskan Native, Native Hawaiian or Other Pacific Islander, South American, Indian, Mexican, Puerto Rican, Creole, Italian/Leonese, Middle Eastern or Spanish. ‘Hispanic’ includes patients who identified as Hispanic or Latino. A CSBM overall responder was defined as a patient with ≥3 CSBMs per week and an increase of ≥1 CSBM per week from baseline for ≥9 of the 12 treatment-period weeks. CSBM, complete spontaneous bowel movement; LIN, linaclotide; PBO, placebo.
Note: The table for this abstract can be viewed in the ePoster Gallery section of the ACG 2024 ePoster Site or in The American Journal of Gastroenterology's abstract supplement issue, both of which will be available starting October 27, 2024.
Baharak Moshiree, MD1, Lin Chang, MD2, Mena Boules, MD3, Wendy Chen, PharmD4, James Wu, PhD3, Moming Li, PhD4, Paul Feuerstadt, MD5, Kyle Staller, MD, MPH6. P2334 - Efficacy and Safety of Linaclotide in Patients With Chronic Idiopathic Constipation: A Post Hoc Analysis of Phase 3 Clinical Study Data Assessing Primary and Additional Endpoints by Race and Ethnicity, and by Age, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
